Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells - PubMed (original) (raw)

. 2013 Dec 19;504(7480):446-50.

doi: 10.1038/nature12721. Epub 2013 Nov 13.

Yuuki Obata 2, Shinji Fukuda 3, Takaho A Endo 4, Gaku Nakato 4, Daisuke Takahashi 4, Yumiko Nakanishi 5, Chikako Uetake 4, Keiko Kato 6, Tamotsu Kato 4, Masumi Takahashi 4, Noriko N Fukuda 5, Shinnosuke Murakami 5, Eiji Miyauchi 4, Shingo Hino 7, Koji Atarashi 8, Satoshi Onawa 4, Yumiko Fujimura 9, Trevor Lockett 10, Julie M Clarke 10, David L Topping 10, Masaru Tomita 5, Shohei Hori 4, Osamu Ohara 4, Tatsuya Morita 7, Haruhiko Koseki 11, Jun Kikuchi 12, Kenya Honda 13, Koji Hase 14, Hiroshi Ohno 11

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Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells

Yukihiro Furusawa et al. Nature. 2013.

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Abstract

Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.

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